Autoimmune disease is caused by an immune response to the antigen of one's own tissue. Alternatively, it occurs when an exogenous organism inhabiting one's body, or a product of the organism, is recognized as an antigen, and an immune response is induced to it. A hidden antigen which normally does not appear in the circulating blood, but is separated from immunocompetent cells, such as cerebral tissue, lens, thyroglobulin or sperm, may be released into the bloodstream by some trigger. Although being one's own body constituent, such a hidden antigen induces an immune response, eventually causing a pathologic state. Autoantibodies can easily develop against many intracellular constituents, but antibodies do not pass through the cell membrane, and thus do no harm to the tissue. Generally, the body is immunologically tolerant to self constituents, and undergoes no autoimmunity. Upon breakdown of immunological tolerance, however, autoantibodies may develop or cellular immunity to self may occur, causing a disease state. Many diseases have now been found to be such autoimmune diseases.
To treat autoimmune disease, corticosteroids or immunosuppressants are effective. To enhance the therapeutic effect of these drugs, early diagnosis of the disease is crucial. With ulcerative colitis or Crohn's disease, endoscopic examination is required for final diagnosis, and a simpler and safer method of diagnosis is demanded. A method by which the pathophysiology or progression of the disease can be known easily over time, if any, would be highly useful.
In autoimmune disease, production of various autoantibodies is considered an important phenomenon characterizing the disease. The mechanism which recognizes various antigens making up self's constituents and produces antibodies corresponding to them has not been thoroughly clarified yet. However, there have been attempts to use this mechanism for the diagnosis of autoimmune disease and the elucidation of its pathophysiology or etiology. Up to now, a considerable number of autoantibodies have been pointed out as having relation to particular autoimmune diseases. For the diagnosis of a certain type of autoimmune disease, screening for the corresponding autoantibodies is an inevitable test. Examples in actual practice are diagnosis of collagen disease using antinuclear antibodies, diagnosis of systemic lupus erythematosus using anti-dsDNA antibodies, diagnosis of scleroderma using autoantibodies to topoisomerase I, and diagnosis of primary biliary cirrhosis using antibodies to mitochondria-derived constituents.
The presence of IgG Fc binding protein, a protein binding specifically to the Fc region of immunoglobulin G or IgG, (Fc.gamma.BP: May be described as Fc.gamma. Binding Protein or IgGFcBP) has been reported by Kobayashi, one the present inventors, and colleagues (Kobayashi, K. et al., J. Immunol., 143:2567-2574, 1989). Specific binding of this protein to the IgG Fc region has been confirmed using a horseradish peroxidase (HRP)-labeled material. That is, Fc.gamma.BP binds only to the Fc region of IgG, but does not bind to IgGFab, IgA or IgM. Nor does Fc.gamma.BP cross-react with anti-Fc.gamma. receptor :, II or III antibodies. Kobayashi et al. further partially purified Fc.gamma.BP from human large intestine epithelial cells, and prepared mouse monoclonal antibodies using it as an antigen. They confirmed these antibodies to bind to mouse IgG as well as to Fc.gamma.BP (Kobayashi, K. et al., J. Immunol., 143:2567-2574, 1989; Kobayashi, K. et al., J. Immunol., 146:68-74, 1991). Morikawa, one the inventors, and colleagues cloned cDNA for Fc.gamma.BP with the use of monoclonal antibodies to Fc.gamma.BP, and clarified the nucleotide sequence of the gene encoding Fc.gamma.BP (Japanese Patent Application No. 109927/95). To date, however, no reports have boon made of the relation between Fc.gamma.BP and autoimmune disease.
As described above, autoantibodies are important for the diagnosis of autoimmune diseases. However, the relationship between various autoimmune diseases and the corresponding autoantibodies is not absolute, and the antibody positive rates of these diseases are various. In some of the diseases, they are low. One kind of antibody may be detected in some diseases. Thus, to diagnose autoimmune diseases reliably, it is desirable to base their diagnosis on combinations of a plurality of autoantibodies, factors potentially regulating their amounts, and clinical findings.